Cerebrovasodilatation through selective inhibition of the enzyme carbonic anhydrase. 3. 5-(Arylthio)-, 5-(arylsulfinyl)-, and 5-(arylsulfonyl)thiophene-2-sulfonamides.
A series of 5-(arylthio)-, 5-(arylsulfinyl)-, and 5-(arylsulfonyl)thiophene-2-sulfonamides is described and anticonvulsant activities are listed for the compounds. In most cases, the sulfones had the highest activity and the sulfides the least. Sulfones with 3- or 4-halo substituents generally had the highest activity, and one analogue, 5-[(4-fluorophenyl)sulfonyl]thiophene-2-sulfonamide (51, UK-17022), had an anticonvulsant ED50 fo 2 mg/kg when administered orally to mice. Compound 51 selectively increased cerebral blood flow in animals without an unacceptable level of diuresis.
D000818:Animals; D000927:Anticonvulsants; D001921:Brain / Q000098:blood supply / Q000201:enzymology; D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases / Q000378:metabolism; D004912:Erythrocytes / Q000201:enzymology; D008297:Male; D051379:Mice; D012039:Regional Blood Flow; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D000927:Anticonvulsants; D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D013876:Thiophenes; D002256:Carbonic Anhydrases